DNA is looked upon as the most critical target of ionizing radiation in
living cells. The prominent types of lesions are DNA single (SSBs) and double
strand breaks (DSBs). The DNA double-strand break (DSB) is regarded as the
essential type of lesion. Both SSBs and DSBs are introduced and resealed regularly
by enzymatic processes during the life cycle of cellular DNA. Incorrect repair
of radiation induced DSBs may result in hazardous consequences like mutations,
transformations or even mitotic death of the cell. However,
DSBs do not represent an uniform species of damage. Either the phosphate or
the sugar moiety may be damaged, and the spatial distribution of the two opposite
ruptures in the sugar-phosphate backbone varies, too.

In the last years, radiation research has focused on the unveiling
of the exact molecular nature of radiation induced DNA damage. Many different experimental
methods are in use today to detect and quantify DNA double-strand breaks, but
all these methods have in common the inability to differentiate specific types
of lesions in individual molecules. They only detect effects by integration
over many identical molecules (&gt 10^7), but qualitative differences in the
damage induction as proposed between low- and high-LET radiation can not be
detected with conventional experimental methods currently available. Refined
microscopic techniques like Scanning Tunneling Microscopy (STM) offer new possibilities.

Applying Scanning Tunneling Microscopy, the possibility of imaging
individual molecules and getting a realistic visual impression of radiation
defects was investigated. A pocked-sized STM was employed which provides atomic
resolution. DNA was dissolved in aqueous solution, dropped onto a layer of highly
oriented graphite and dried in air. Tunneling tips consisted of tungsten-wires
that were mechanically cut or chemically etched. Scanning Tunneling Microscopy
of the specimen was always performed under atmospheric conditions to avoid influences
onto the biological sample.

(You may download it, provided you refer to the
author and GSI when published. Unfortunately we don't have this picture with
a better resolution, this was a limitation of the data taking procedure)

With purified salmon sperm DNA, high resolution images were obtained
allowing the determination of the dimensions of the DNA double helix. The apparent
diameter of the DNA molecule shown here is about 2 nm, in excellent agreement
with the expected value. The molecule is right-handed and the helix pitch amounts
to 3.3 nm.

The primary purpose of our investigations is the visualisation
of DNA lesions. For further experiments, focusing on the observation of X-ray
induced damages, plasmid DNA was used as specimen. After X-irradiation significantly
conformational changes could be observed with STM. With technical advances,
STM may become a versatile analytical requisite for the qualitative analysis
of high- and low-LET DNA damage on the molecular level.